CA3217649A1 - Vecteurs aavrh74 de therapie genique de dystrophies musculaires - Google Patents
Vecteurs aavrh74 de therapie genique de dystrophies musculaires Download PDFInfo
- Publication number
- CA3217649A1 CA3217649A1 CA3217649A CA3217649A CA3217649A1 CA 3217649 A1 CA3217649 A1 CA 3217649A1 CA 3217649 A CA3217649 A CA 3217649A CA 3217649 A CA3217649 A CA 3217649A CA 3217649 A1 CA3217649 A1 CA 3217649A1
- Authority
- CA
- Canada
- Prior art keywords
- sequence
- aavrh74
- itr
- seq
- nucleic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000013598 vector Substances 0.000 title claims abstract description 258
- 201000006938 muscular dystrophy Diseases 0.000 title claims description 13
- 238000001415 gene therapy Methods 0.000 title description 12
- 239000002245 particle Substances 0.000 claims abstract description 188
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 163
- 108090000565 Capsid Proteins Proteins 0.000 claims abstract description 154
- 102100023321 Ceruloplasmin Human genes 0.000 claims abstract description 154
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 144
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 144
- 238000000034 method Methods 0.000 claims abstract description 67
- 239000000203 mixture Substances 0.000 claims abstract description 41
- 210000004027 cell Anatomy 0.000 claims description 142
- 238000006467 substitution reaction Methods 0.000 claims description 120
- 239000002773 nucleotide Substances 0.000 claims description 107
- 125000003729 nucleotide group Chemical group 0.000 claims description 107
- 230000002441 reversible effect Effects 0.000 claims description 84
- 238000010361 transduction Methods 0.000 claims description 60
- 230000026683 transduction Effects 0.000 claims description 53
- 108090000623 proteins and genes Proteins 0.000 claims description 49
- 230000000295 complement effect Effects 0.000 claims description 42
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 23
- 210000001519 tissue Anatomy 0.000 claims description 23
- 208000029578 Muscle disease Diseases 0.000 claims description 21
- 210000002363 skeletal muscle cell Anatomy 0.000 claims description 20
- 238000004806 packaging method and process Methods 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- 230000001105 regulatory effect Effects 0.000 claims description 13
- 230000035772 mutation Effects 0.000 claims description 12
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 11
- 102000003676 Glucocorticoid Receptors Human genes 0.000 claims description 11
- 108090000079 Glucocorticoid Receptors Proteins 0.000 claims description 11
- 238000001727 in vivo Methods 0.000 claims description 10
- 208000021642 Muscular disease Diseases 0.000 claims description 8
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims description 7
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 claims description 7
- 238000000338 in vitro Methods 0.000 claims description 7
- 230000001939 inductive effect Effects 0.000 claims description 7
- 208000013896 centronuclear myopathy X-linked Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 210000000663 muscle cell Anatomy 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 108010069091 Dystrophin Proteins 0.000 claims description 4
- 108091027981 Response element Proteins 0.000 claims description 4
- 208000032978 Structural Congenital Myopathies Diseases 0.000 claims description 4
- 208000025033 X-linked centronuclear myopathy Diseases 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims description 3
- 201000009623 Myopathy Diseases 0.000 claims description 3
- 201000002481 Myositis Diseases 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 239000003623 enhancer Substances 0.000 claims description 3
- 230000000977 initiatory effect Effects 0.000 claims description 3
- 239000012212 insulator Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 210000004962 mammalian cell Anatomy 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 3
- 210000001874 anterior cell Anatomy 0.000 claims description 2
- 239000007928 intraperitoneal injection Substances 0.000 claims description 2
- 101150088768 mtm-1 gene Proteins 0.000 claims description 2
- 230000003584 silencer Effects 0.000 claims description 2
- 238000010254 subcutaneous injection Methods 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 7
- 230000014509 gene expression Effects 0.000 description 81
- 108700019146 Transgenes Proteins 0.000 description 77
- 150000001413 amino acids Chemical group 0.000 description 50
- 235000001014 amino acid Nutrition 0.000 description 47
- 230000004048 modification Effects 0.000 description 40
- 238000012986 modification Methods 0.000 description 40
- 238000012217 deletion Methods 0.000 description 31
- 230000037430 deletion Effects 0.000 description 31
- 210000000234 capsid Anatomy 0.000 description 27
- 108091028043 Nucleic acid sequence Proteins 0.000 description 21
- 210000003205 muscle Anatomy 0.000 description 19
- CSEBNABAWMZWIF-UHFFFAOYSA-N 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid Chemical compound OC(=O)C(F)(C(F)(F)F)OC(F)(F)C(F)(F)C(F)(F)F CSEBNABAWMZWIF-UHFFFAOYSA-N 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 14
- 201000010099 disease Diseases 0.000 description 12
- 230000001976 improved effect Effects 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 12
- 108020004414 DNA Proteins 0.000 description 11
- 238000011161 development Methods 0.000 description 11
- -1 genomes Proteins 0.000 description 11
- 229920001184 polypeptide Polymers 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- 101710132601 Capsid protein Proteins 0.000 description 9
- 101710197658 Capsid protein VP1 Proteins 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 101710108545 Viral protein 1 Proteins 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 239000005090 green fluorescent protein Substances 0.000 description 9
- 108020004999 messenger RNA Proteins 0.000 description 9
- 238000011002 quantification Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 239000013607 AAV vector Substances 0.000 description 7
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 7
- 101000805768 Banna virus (strain Indonesia/JKT-6423/1980) mRNA (guanine-N(7))-methyltransferase Proteins 0.000 description 7
- 101000686790 Chaetoceros protobacilladnavirus 2 Replication-associated protein Proteins 0.000 description 7
- 101000864475 Chlamydia phage 1 Internal scaffolding protein VP3 Proteins 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 7
- 101000803553 Eumenes pomiformis Venom peptide 3 Proteins 0.000 description 7
- 101000583961 Halorubrum pleomorphic virus 1 Matrix protein Proteins 0.000 description 7
- 101710081079 Minor spike protein H Proteins 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 6
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 6
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 6
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 230000003362 replicative effect Effects 0.000 description 6
- 230000000007 visual effect Effects 0.000 description 6
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 5
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 210000000188 diaphragm Anatomy 0.000 description 5
- 238000002073 fluorescence micrograph Methods 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 238000012423 maintenance Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 241000649045 Adeno-associated virus 10 Species 0.000 description 4
- 241000649046 Adeno-associated virus 11 Species 0.000 description 4
- 241000649047 Adeno-associated virus 12 Species 0.000 description 4
- 102100024108 Dystrophin Human genes 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 241000300529 Adeno-associated virus 13 Species 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 108010082025 cyan fluorescent protein Proteins 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000000799 fluorescence microscopy Methods 0.000 description 3
- 108091006047 fluorescent proteins Proteins 0.000 description 3
- 102000034287 fluorescent proteins Human genes 0.000 description 3
- 238000010362 genome editing Methods 0.000 description 3
- 210000005003 heart tissue Anatomy 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000009145 protein modification Effects 0.000 description 3
- 108010054624 red fluorescent protein Proteins 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000012384 transportation and delivery Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 102100032539 Calpain-3 Human genes 0.000 description 2
- 102100032212 Caveolin-3 Human genes 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 102100035425 DnaJ homolog subfamily B member 6 Human genes 0.000 description 2
- 102100029503 E3 ubiquitin-protein ligase TRIM32 Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 101000867715 Homo sapiens Calpain-3 Proteins 0.000 description 2
- 101000869042 Homo sapiens Caveolin-3 Proteins 0.000 description 2
- 101000804112 Homo sapiens DnaJ homolog subfamily B member 6 Proteins 0.000 description 2
- 101000634982 Homo sapiens E3 ubiquitin-protein ligase TRIM32 Proteins 0.000 description 2
- 101001030184 Homo sapiens Myotilin Proteins 0.000 description 2
- 101001132874 Homo sapiens Myotubularin Proteins 0.000 description 2
- 101001003584 Homo sapiens Prelamin-A/C Proteins 0.000 description 2
- 101000645320 Homo sapiens Titin Proteins 0.000 description 2
- 102000006830 Luminescent Proteins Human genes 0.000 description 2
- 108010047357 Luminescent Proteins Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100038894 Myotilin Human genes 0.000 description 2
- 102100033817 Myotubularin Human genes 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 102100026531 Prelamin-A/C Human genes 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 102100026260 Titin Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 108091005948 blue fluorescent proteins Proteins 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 108010021843 fluorescent protein 583 Proteins 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- ZQFURSYWJPLAJR-UHFFFAOYSA-N (3E)-1-methoxy-3,4-didehydro-1,2,7',8'-tetrahydro-psi,psi-caroten-2-one Chemical compound COC(C)(C)C(=O)C=CC(C)=CC=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)CCC=C(C)CCC=C(C)C ZQFURSYWJPLAJR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 102100026656 Actin, alpha skeletal muscle Human genes 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 241000059559 Agriotes sordidus Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100030685 Alpha-sarcoglycan Human genes 0.000 description 1
- 241000282709 Aotus trivirgatus Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000282672 Ateles sp. Species 0.000 description 1
- 208000035913 Atypical hemolytic uremic syndrome Diseases 0.000 description 1
- 108091005950 Azurite Proteins 0.000 description 1
- 201000006935 Becker muscular dystrophy Diseases 0.000 description 1
- 102100030686 Beta-sarcoglycan Human genes 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102100035475 Blood vessel epicardial substance Human genes 0.000 description 1
- 101710174254 Blood vessel epicardial substance Proteins 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010051093 Cardiopulmonary failure Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108091005944 Cerulean Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 241000862448 Chlorocebus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010023936 Cofilin 2 Proteins 0.000 description 1
- 102100027440 Cofilin-2 Human genes 0.000 description 1
- 102100031519 Collagen alpha-1(VI) chain Human genes 0.000 description 1
- 102100031518 Collagen alpha-2(VI) chain Human genes 0.000 description 1
- 102100024338 Collagen alpha-3(VI) chain Human genes 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108091005943 CyPet Proteins 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102100031515 D-ribitol-5-phosphate cytidylyltransferase Human genes 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102100021790 Delta-sarcoglycan Human genes 0.000 description 1
- 102100036912 Desmin Human genes 0.000 description 1
- 108010044052 Desmin Proteins 0.000 description 1
- 102100021158 Double homeobox protein 4 Human genes 0.000 description 1
- 108010044191 Dynamin II Proteins 0.000 description 1
- 102000020630 Dynamin II Human genes 0.000 description 1
- 102100032248 Dysferlin Human genes 0.000 description 1
- 102100025682 Dystroglycan 1 Human genes 0.000 description 1
- 108091005941 EBFP Proteins 0.000 description 1
- 108091005947 EBFP2 Proteins 0.000 description 1
- 108091005942 ECFP Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 208000037149 Facioscapulohumeral dystrophy Diseases 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102100021792 Gamma-sarcoglycan Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102100027706 Heterogeneous nuclear ribonucleoprotein D-like Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000834207 Homo sapiens Actin, alpha skeletal muscle Proteins 0.000 description 1
- 101000703500 Homo sapiens Alpha-sarcoglycan Proteins 0.000 description 1
- 101000703495 Homo sapiens Beta-sarcoglycan Proteins 0.000 description 1
- 101000941581 Homo sapiens Collagen alpha-1(VI) chain Proteins 0.000 description 1
- 101000941585 Homo sapiens Collagen alpha-2(VI) chain Proteins 0.000 description 1
- 101000909506 Homo sapiens Collagen alpha-3(VI) chain Proteins 0.000 description 1
- 101000994204 Homo sapiens D-ribitol-5-phosphate cytidylyltransferase Proteins 0.000 description 1
- 101000616408 Homo sapiens Delta-sarcoglycan Proteins 0.000 description 1
- 101000968549 Homo sapiens Double homeobox protein 4 Proteins 0.000 description 1
- 101001016184 Homo sapiens Dysferlin Proteins 0.000 description 1
- 101000855983 Homo sapiens Dystroglycan 1 Proteins 0.000 description 1
- 101001053946 Homo sapiens Dystrophin Proteins 0.000 description 1
- 101000616435 Homo sapiens Gamma-sarcoglycan Proteins 0.000 description 1
- 101001081145 Homo sapiens Heterogeneous nuclear ribonucleoprotein D-like Proteins 0.000 description 1
- 101000974775 Homo sapiens Kelch repeat and BTB domain-containing protein 13 Proteins 0.000 description 1
- 101000945199 Homo sapiens Kelch-like protein 30 Proteins 0.000 description 1
- 101001027192 Homo sapiens Kelch-like protein 41 Proteins 0.000 description 1
- 101001042354 Homo sapiens LIM and senescent cell antigen-like-containing domain protein 2 Proteins 0.000 description 1
- 101000972491 Homo sapiens Laminin subunit alpha-2 Proteins 0.000 description 1
- 101001135070 Homo sapiens Leiomodin-3 Proteins 0.000 description 1
- 101001040781 Homo sapiens Mannose-1-phosphate guanyltransferase beta Proteins 0.000 description 1
- 101000982003 Homo sapiens Myopalladin Proteins 0.000 description 1
- 101001030243 Homo sapiens Myosin-7 Proteins 0.000 description 1
- 101001126471 Homo sapiens Plectin Proteins 0.000 description 1
- 101001123963 Homo sapiens Protein O-mannosyl-transferase 1 Proteins 0.000 description 1
- 101001094684 Homo sapiens Protein O-mannosyl-transferase 2 Proteins 0.000 description 1
- 101000846198 Homo sapiens Ribitol 5-phosphate transferase FKRP Proteins 0.000 description 1
- 101000846336 Homo sapiens Ribitol-5-phosphate transferase FKTN Proteins 0.000 description 1
- 101000693993 Homo sapiens Sodium channel protein type 4 subunit alpha Proteins 0.000 description 1
- 101000597193 Homo sapiens Telethonin Proteins 0.000 description 1
- 101001008959 Homo sapiens Thymidine kinase 2, mitochondrial Proteins 0.000 description 1
- 101000662695 Homo sapiens Trafficking protein particle complex subunit 11 Proteins 0.000 description 1
- 101000850794 Homo sapiens Tropomyosin alpha-3 chain Proteins 0.000 description 1
- 101000851892 Homo sapiens Tropomyosin beta chain Proteins 0.000 description 1
- 101000851357 Homo sapiens Troponin T, slow skeletal muscle Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102100022803 Kelch repeat and BTB domain-containing protein 13 Human genes 0.000 description 1
- 102100033554 Kelch-like protein 30 Human genes 0.000 description 1
- 102100037644 Kelch-like protein 41 Human genes 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 102100021755 LIM and senescent cell antigen-like-containing domain protein 2 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
- 102100033509 Leiomodin-3 Human genes 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100021171 Mannose-1-phosphate guanyltransferase beta Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 102100026786 Myopalladin Human genes 0.000 description 1
- 102100038934 Myosin-7 Human genes 0.000 description 1
- 108010052185 Myotonin-Protein Kinase Proteins 0.000 description 1
- 102100022437 Myotonin-protein kinase Human genes 0.000 description 1
- 102100034434 Nebulin Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100023421 Nuclear receptor ROR-gamma Human genes 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 241000522587 Oplophorus gracilirostris Species 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102100030477 Plectin Human genes 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- 102100036226 Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 Human genes 0.000 description 1
- 102100028120 Protein O-mannosyl-transferase 1 Human genes 0.000 description 1
- 102100035490 Protein O-mannosyl-transferase 2 Human genes 0.000 description 1
- 108091008773 RAR-related orphan receptors γ Proteins 0.000 description 1
- 102000004913 RYR1 Human genes 0.000 description 1
- 108060007240 RYR1 Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 0.000 description 1
- 102100031774 Ribitol 5-phosphate transferase FKRP Human genes 0.000 description 1
- 102100031754 Ribitol-5-phosphate transferase FKTN Human genes 0.000 description 1
- 101001053942 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Diphosphomevalonate decarboxylase Proteins 0.000 description 1
- 241000288961 Saguinus imperator Species 0.000 description 1
- 241000282695 Saimiri Species 0.000 description 1
- 241001635911 Sarepta Species 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102100027195 Sodium channel protein type 4 subunit alpha Human genes 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- AXDLADCVDYBQBY-XRKCEDLHSA-N Spheroidenone Natural products COC(C)(C)C(=O)C=CC(=CC=CC(=CC=CC(=CC=CC=CC(C)C=C/C=C(C)/CCC=C(/C)CC=C(C)C)C)C)C AXDLADCVDYBQBY-XRKCEDLHSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102100035155 Telethonin Human genes 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 102100027624 Thymidine kinase 2, mitochondrial Human genes 0.000 description 1
- 102100037455 Trafficking protein particle complex subunit 11 Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102100033080 Tropomyosin alpha-3 chain Human genes 0.000 description 1
- 102100036471 Tropomyosin beta chain Human genes 0.000 description 1
- 102100036860 Troponin T, slow skeletal muscle Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- IUUXWKRRZDDNQG-UHFFFAOYSA-N all-trans-spheroidene Natural products COC(C)(C)CCCC(C)=CC=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)CCC=C(C)CCC=C(C)C IUUXWKRRZDDNQG-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000005045 desmin Anatomy 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 208000008570 facioscapulohumeral muscular dystrophy Diseases 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000006525 intracellular process Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 108010054130 nebulin Proteins 0.000 description 1
- 238000007481 next generation sequencing Methods 0.000 description 1
- 230000025308 nuclear transport Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108010039031 protein O-mannose beta-1,2-N-acetylglucosaminyltransferase Proteins 0.000 description 1
- 239000013608 rAAV vector Substances 0.000 description 1
- 101150107339 rpsN gene Proteins 0.000 description 1
- 102220132578 rs761410037 Human genes 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 235000001606 spheroiden-2-one Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- XQTLDIFVVHJORV-UHFFFAOYSA-N tecnazene Chemical compound [O-][N+](=O)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl XQTLDIFVVHJORV-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GWBUNZLLLLDXMD-UHFFFAOYSA-H tricopper;dicarbonate;dihydroxide Chemical compound [OH-].[OH-].[Cu+2].[Cu+2].[Cu+2].[O-]C([O-])=O.[O-]C([O-])=O GWBUNZLLLLDXMD-UHFFFAOYSA-H 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
- A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
- A61K48/0041—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being polymeric
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
- C07K14/01—DNA viruses
- C07K14/015—Parvoviridae, e.g. feline panleukopenia virus, human parvovirus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/864—Parvoviral vectors, e.g. parvovirus, densovirus
- C12N15/8645—Adeno-associated virus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14145—Special targeting system for viral vectors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
Abstract
L'invention concerne des protéines de capside de VAA modifiées, des particules, des vecteurs d'acide nucléique et leurs compositions, ainsi que leurs méthodes d'utilisation.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163179097P | 2021-04-23 | 2021-04-23 | |
US63/179,097 | 2021-04-23 | ||
US202263327410P | 2022-04-05 | 2022-04-05 | |
US63/327,410 | 2022-04-05 | ||
PCT/US2022/025916 WO2022226289A2 (fr) | 2021-04-23 | 2022-04-22 | Vecteurs aavrh74 de thérapie génique de dystrophies musculaires |
Publications (1)
Publication Number | Publication Date |
---|---|
CA3217649A1 true CA3217649A1 (fr) | 2022-10-27 |
Family
ID=81648417
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA3217649A Pending CA3217649A1 (fr) | 2021-04-23 | 2022-04-22 | Vecteurs aavrh74 de therapie genique de dystrophies musculaires |
Country Status (11)
Country | Link |
---|---|
US (1) | US20220347317A1 (fr) |
EP (1) | EP4326857A2 (fr) |
JP (1) | JP2024514962A (fr) |
KR (1) | KR20240000542A (fr) |
AU (1) | AU2022262407A1 (fr) |
BR (1) | BR112023021495A2 (fr) |
CA (1) | CA3217649A1 (fr) |
CO (1) | CO2023015911A2 (fr) |
IL (1) | IL307881A (fr) |
TW (1) | TW202304954A (fr) |
WO (1) | WO2022226289A2 (fr) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2839014B1 (fr) * | 2012-04-18 | 2020-12-16 | The Children's Hospital of Philadelphia | Composition et procédés pour un transfert génique hautement efficace à l'aide de variants de capside aav |
EP3221456B1 (fr) | 2014-11-21 | 2021-09-22 | University of Florida Research Foundation, Inc. | Vecteurs viraux adéno-associés recombinés au génome modifié |
-
2022
- 2022-04-22 IL IL307881A patent/IL307881A/en unknown
- 2022-04-22 WO PCT/US2022/025916 patent/WO2022226289A2/fr active Application Filing
- 2022-04-22 CA CA3217649A patent/CA3217649A1/fr active Pending
- 2022-04-22 US US17/727,007 patent/US20220347317A1/en active Pending
- 2022-04-22 AU AU2022262407A patent/AU2022262407A1/en active Pending
- 2022-04-22 TW TW111115475A patent/TW202304954A/zh unknown
- 2022-04-22 BR BR112023021495A patent/BR112023021495A2/pt unknown
- 2022-04-22 EP EP22723290.7A patent/EP4326857A2/fr active Pending
- 2022-04-22 KR KR1020237039756A patent/KR20240000542A/ko unknown
- 2022-04-22 JP JP2023565307A patent/JP2024514962A/ja active Pending
-
2023
- 2023-11-22 CO CONC2023/0015911A patent/CO2023015911A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
EP4326857A2 (fr) | 2024-02-28 |
AU2022262407A1 (en) | 2023-10-26 |
US20220347317A1 (en) | 2022-11-03 |
AU2022262407A9 (en) | 2023-11-09 |
IL307881A (en) | 2023-12-01 |
WO2022226289A3 (fr) | 2023-03-02 |
KR20240000542A (ko) | 2024-01-02 |
JP2024514962A (ja) | 2024-04-03 |
CO2023015911A2 (es) | 2023-11-30 |
BR112023021495A2 (pt) | 2023-12-19 |
TW202304954A (zh) | 2023-02-01 |
WO2022226289A2 (fr) | 2022-10-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11325956B2 (en) | Dual-AAV vector-based systems and methods for delivering oversized genes to mammalian cells | |
JP7452953B2 (ja) | 1色覚および他の疾患の治療のためのプロモーター、発現カセット、ベクター、キット、ならびに方法 | |
US11266748B2 (en) | Recombinant adeno-associated virus vectors to target medullary thyroid carcinoma | |
JP5922095B2 (ja) | 薬理学的に誘導される導入遺伝子アブレーション系 | |
EP2761009B1 (fr) | Système d'ablation de transgène médié par un vecteur viral adéno-associé inductible | |
JP2023503637A (ja) | マイクロジストロフィン遺伝子治療コンストラクト及びその使用 | |
EP3221456A2 (fr) | Vecteurs viraux adéno-associés recombinés au génome modifié | |
KR20220133854A (ko) | 유전적 청력 상실 치료를 위한 아데노 관련 바이러스(aav) 시스템 | |
WO2008021140A2 (fr) | Production de aav recombinant dans des cellules mammaliennes | |
US20020076754A1 (en) | Overcoming AAV vector size limitation through viral DNA hetero-dimerization | |
CN116209768A (zh) | 用于通过高变区交换工程化新杂合aav衣壳的方法 | |
US20240181083A1 (en) | Aavrh74 vectors for gene therapy of muscular dystrophies | |
US20220347317A1 (en) | Aavrh74 vectors for gene therapy of muscular dystrophies | |
US20030190746A1 (en) | Gene expression control system and its use in recombinant virus packaging cell lines | |
JP2023524291A (ja) | 異種間適合性アデノ随伴ウイルス組成物およびその使用方法 | |
CN117355603A (zh) | 用于肌营养不良的基因治疗的aavrh74载体 | |
US11999965B2 (en) | Bocaparvovirus small noncoding RNA and uses thereof | |
JP2007504219A (ja) | 関節リウマチのインビボ遺伝子治療のためのaavベクター | |
WO2023205610A2 (fr) | Capsides aav hybrides | |
WO2023044438A2 (fr) | Particules d'aavrh74 pour la thérapie génique d'une maladie musculaire | |
WO2023044441A1 (fr) | Particules de vaa avec répétitions terminales inversées modifiées pour expression génique accrue dans le muscle | |
WO2022232029A2 (fr) | Vecteurs vaa synthétiques pour l'administration répétée de gènes thérapeutiques | |
Ling | The development of adeno-associated virus serotype 3 vector-based potential gene therapy for human liver cancer |